Refractory GERD: A Consensus Paper for Diagnosing and Managing Patients

A new consensus paper provides 40 statements on many factors of GERD, including clinical features, endoscopy, physiologic investigations, lifestyle interventions, optimizing acid-suppressive therapy, adjunctive medical therapy, and surgical and interventional management.

A position paper released by the European Society for Neurogastroenterology and Motility (ESNM) and the American Neurogastroenterology and Motility Society (ANMS) has addressed clinically relevant issues relating to the effective management of patients with refractory gastroesophageal reflux disease (GERD).

The consensus paper, published in Neurogastroenterology & Motility,1 includes 40 statements that focus on many aspects of GERD, including clinical features, endoscopy, physiologic investigations, lifestyle interventions, optimizing acid-suppressive therapy, adjunctive medical therapy, and surgical and interventional management.

A distinction is needed among refractory symptoms (ie, symptoms may be GERD-related), refractory GERD symptoms, and refractory GERD, according to the position paper. The paper’s first statement defined refractory GERD symptoms as “the persistence of symptoms on therapy in patients with prior objective evidence of GERD (erosive esophagitis, peptic stricture, long-segment Barrett’s esophagus, or abnormal esophageal acid exposure on reflux monitoring performed off therapy).”

The paper’s authors defined refractory GERD as “persisting objective GERD evidence despite medical therapy (erosive esophagitis, or abnormal esophageal acid exposure and/or elevated numbers of reflux episodes on reflux monitoring performed on therapy).”

Refractory GERD symptoms are partially responsive or nonresponsive to a stable dose of a proton pump inhibitor (PPI) during treatment of at least 8 weeks in patients with prior objective evidence of GERD, according to the consensus paper’s authors.

In diagnosing patients with proven GERD, persistent typical symptoms and atypical symptoms (noncardiac chest pain, extraesophageal symptoms) in the setting of PPI therapy deserve further assessment for poorly controlled GERD, functional esophageal disorders, motility disorders, and specific pulmonary or pharyngo-laryngeal etiologies, as appropriate, according to the authors.

“While persistent symptoms of heartburn or non-cardiac chest pain may represent poorly controlled GERD, they are often due to an overlap with a functional esophageal disorder through mechanisms of visceral hypersensitivity and hypervigilance,” stated the position paper authors. “Functional heartburn, functional chest pain, or reflux hypersensitivity explain persistent symptoms in up to 75% of patients with GERD.”

In patients with proven GERD and a large hiatal hernia, persistent regurgitation on PPI therapy is likely to be related to refractory GERD, according to the paper.

“Refractory GERD symptoms can be both typical (ie, heartburn and regurgitation) and/or atypical (chest pain, laryngo-pharyngeal, pulmonary), but the probability that poorly controlled GERD is the underlying cause of atypical symptoms is much lower compared to typical symptoms,” the authors commented.

According to the position paper, Los Angeles grade B/C/D esophagitis on endoscopy despite optimized PPI therapy is indicative of refractory GERD. In patients who have refractory GERD symptoms, nonspecific inflammation on esophageal biopsy specimens is not relevant, and the diagnostic yield of eosinophilic esophagitis is very low in the absence of dysphagia and specific endoscopic signs. In addition, Barrett mucosa of any length does not indicate poor GERD control, noted the authors.

“Endoscopic and/or radiologic evaluation of esophagogastric junction morphology should be performed in patients with refractory GERD symptoms,” advised the authors.

The position paper recommends that patients with persistent esophageal or extraesophageal symptoms on PPI therapy and no previously documented GERD should be investigated with endoscopy and ambulatory pH or pH-impedance monitoring off therapy to document the presence or absence of baseline abnormal reflux.

“In patients with proven GERD and persistent symptoms on PPI therapy, esophageal manometry and 24-hour pH-impedance on therapy are requisite to distinguish refractory GERD from functional esophageal disorders,” stated the authors.

The guideline recommended that esophageal motility should be assessed using high-resolution manometry in patients with refractory GERD symptoms. High-resolution manometry can rule out major esophageal motility disorders and demonstrate esophagogastric junction and esophageal body motor abnormalities associated with GERD, noted the paper’s authors. In asymptomatic patients with untreated Barrett esophagus, testing for persisting reflux in the setting of PPI therapy is not recommended, according to the paper.

Among lifestyle interventions for GERD, weight loss reduces esophageal acid exposure and reflux symptoms, even in nonobese patients with GERD. Evidence is insufficient to assess the value of smoking cessation or discontinuation of alcohol consumption in treating patients with refractory GERD symptoms, the authors noted.

“Symptomatic GERD patients should be recommended postural measures, including avoiding eating dinner close to bedtime, elevation of the head end of the bed by at least 20 cm, and sleeping in the left lateral position using sleep positional therapy,” they advised.

The consensus paper also recommended steps to optimize the use of acid-suppressive therapy.

“PPIs are more effective in reducing GERD symptoms when taken before meals, before breakfast with once-daily dosing, and before breakfast and 30 to 60 minutes before dinner with twice-daily dosing,” according to the paper. “The subset of refractory GERD patients with persistent esophagitis on endoscopy or persistent esophageal acid exposure on pH monitoring should be treated with a more potent PPI regimen.”

Regarding the use of adjunctive medical therapy, the position paper advised that short-term nighttime H2 receptor antagonists (H2RAs) can be considered for patients with refractory nocturnal reflux symptoms, but it cautioned that the evidence is indirect and limited. The paper’s authors added that prokinetics have no added value for treating patients with PPI refractory reflux symptoms, and baclofen has proven efficacy in PPI-refractory GERD, although adverse effects often limit its use. In addition, some evidence suggests that topical mucosal preparations containing alginate as well as protective agents reduce symptoms in patients with PPI-refractory GERD.

The position paper recommended that antireflux surgery, including laparoscopic fundoplication and magnetic sphincter augmentation, improves refractory GERD symptoms, particularly regurgitation, in patients with proven GERD. Some research has shown that laparoscopic fundoplication is comparable to long-term PPI therapy in well-characterized GERD.

“Obese patients with refractory GERD can benefit from Roux-en-Y gastric bypass surgery, which effectively disconnects the esophagus from the body of the stomach and reliably reduces esophageal reflux burden, while also ensuring weight loss,” stated the paper’s authors. “Roux-en-Y bypass surgery is safer than laparoscopic fundoplication in morbidly obese patients, with less postoperative complications, despite similar hospital costs, length of stay, and mortality.”

Also, transoral incisionless fundoplication has shown short-term and limited longer-term benefit for improving regurgitation in some patients.

“While persisting symptoms are frequently encountered during PPI therapy of esophageal symptoms, not all refractory symptoms represent refractory GERD,” the authors advised.

“Understanding the epidemiology of refractory GERD as opposed to refractory GERD symptoms and the pharmacotherapeutics of antisecretory therapy will help the clinician select the optimal approach to refractory symptoms and determine the most efficient testing modalities that will help plan an effective management approach,” the authors commented. “Along the way, conditions that mimic GERD are diagnosed and appropriately managed, and refractory GERD is appropriately addressed with optimized medical or procedural therapy.”

The consensus paper expanded on clinical data and expert review published since the Montreal Consensus2 to include concepts described in the ROME IV document on functional esophageal disorders3 and the Lyon consensus establishing criteria for conclusive GERD.4 The ESNM and the ANMS jointly commissioned and endorsed the paper.

Disclosures: Some of the authors reported affiliations with pharmaceutical and medical device companies. Please see the original reference for a full list of disclosures.

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1. Zerbib Z, Bredenoord AJ, Fass R, et al. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux diseaseNeurogastroenterol Motil. Published online December 28, 2020. doi:10.1111/nmo.14075

2. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-1920; quiz 1943.

3. Aziz Q, Fass R, Gyawali CP, et al. Esophageal disorders. Gastroenterology. 2016;150(6):P1368-P1379.

4. Gyawali CP, Kahrilas PJ, Savarino E, et al. Modern diagnosis of GERD: the Lyon consensus. Gut. 2018;67(7):1351-1362.